PROJECT SUMMARY ? RADIATION BIOLOGY PROGRAM The Program in Radiation Biology is focused on ways in which the effectiveness of radiotherapy can increase both local tumor control and the survival of cancer patients. The members of this program investigate new ways to enhance the efficacy of radiotherapy by targeting the tumor microenvironment, protecting normal tissue from radiation toxicity, and developing new technology to deliver radiation in a focused manner at high speed. To achieve these goals, basic discovery science, high throughput screening and preclinical models are used to obtain critical supporting data to take these approaches into clinical trials. Thus, the program includes both basic and translational science. Program research is focused on two major scientific aims: Aim 1: To develop pharmacologic and biologic agents to combine with radiotherapy to improve local tumor control and prevent metastatic spread. These studies are focused on developing new approaches to improve local control with radiotherapy, protect normal tissues from radiation toxicity, and identify genetic determinants that influence the response of tumors to DNA damage and modulate tissue integrity. Aim 2: To develop new approaches to administer radiotherapy or combined modality therapy to test in clinical trials. These investigations employ diverse approaches that include the use of functional imaging to more selectively deliver radiotherapy, expand the uses of hypofractionated radiotherapy, and develop new technologies that can deliver high-energy electrons in less than a second. The program is co-led by Amato Giaccia, PhD and Quynh Le, MD. The 25 members of this program represent the School of Medicine and the School of Humanities and Sciences, and are supported by peer-reviewed research totaling $8.0M, including 21 R01s, 1P01s, and 2 T32s. Peer-reviewed funding consists of $4.7M from the NCI, other NIH support amounts to $2.5M, and other peer-reviewed support to $0.9M. The members of this program are highly motivated and interactive in their goal to take fundamental discoveries in the laboratory and develop them to increase the efficacy of radiotherapy to control tumor growth and metastasis. Since 2009, members of the Radiation Biology Program published 450 manuscripts, a near doubling from the last submission. Of these, 31% represent intra- programmatic collaborations and 33% represent inter-programmatic collaborations. The Stanford Cancer Institute enhances the program's goals by providing state-of-the-art shared resources, seed grant support for new projects, programmatic funds, retreats, special seminars, and support for new recruitments. The support from the SCI has been instrumental in promoting both intra- and inter- programmatic collaborations that were essential for the renewal of our program project grant on tumor hypoxia, the development of a new program project grant on tissue radioprotection, and the renewal of our T32 training grant to train postdoctoral fellows.